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Direct intraarterial wall injection of microparticles via a catheter: a potential drug delivery strategy following angioplasty.

Local delivery into the arterial wall of medications at high concentrations may evolve as a method to reduce postangioplasty restenosis. However, since the atherosclerotic artery has increased vasa vasorum, medications injected in a fluid state may diffuse out of the arterial wall too quickly to have a therapeutic effect. Thus we evaluated whether microparticles as a model for a particulate microcarrier drug delivery system, injected via a porous balloon catheter, could be retained within the atherosclerotic rabbit femoral arterial wall. Arteries were injected with a 5 microns microparticle suspension for 45 seconds at either 3 or 5 atm of infusion pressure immediately following balloon angioplasty. Arteries were obtained immediately following the procedure or at 1, 3, 7, or 14 days after infusion to evaluate for the presence of retained microparticles. Of 34 arteries, 30 contained retained microparticles, with 21 exhibiting microparticles in the neointimia, 12 in the media, and 25 in the adventitia. Microparticles were retained for as long as 14 days, and there was no difference between the distribution or quantity of microparticles at 3 or 5 atm of infusion pressure. The mode of microparticle distribution probably involved deposition within dissection planes, although evidence for vasa vasorum transport was observed. We hypothesize that biodegradable microparticles could serve as a vehicle for intramural drug delivery in the treatment of restenosis.

Angioplasty, Balloon↗

Role of the bronchial circulation in ischemia-reperfusion lung injury.

Bronchial arterial (BA) perfusion could modify pulmonary arterial (PA) ischemia-reperfusion (IR) injury by promoting clearance of peribronchial edema or limiting edema formation through maintenance of pulmonary vessel integrity via bronchopulmonary anastomotic or pulmonary vasa vasorum flow. The purpose of this study was to determine the effect of BA perfusion on IR injury in isolated sheep lungs. In 12 lungs (BA++) the BA was perfused throughout 30 min of PA ischemia and 180 min of reperfusion. In 12 lungs (BA-+) BA perfusion was begun with PA reperfusion, and in 15 lungs (BA--) the BA was never perfused. After 180 min, extravascular lung water was less (P < 0.05) in BA++ and B-+ lungs [4.70 +/- 0.16 and 4.57 +/- 0.18 g/g blood-free dry lung (bfdl)] than in BA-- lungs (5.23 +/- 0.19 g/g bfdl). The reflection coefficient for albumin was greater (P < 0.05) in BA++ and BA-+ (0.57 +/- 0.06 and 0.75 +/- 0.03) than in BA-- lungs (0.44 +/- 0.04). The filtration coefficient in BA++ and BA-+ lungs (0.016 +/- 0.006 and 0.015 +/- 0.006 g.min-1 x mmHg-1 x kg-1) was not different from that in BA-- lungs (0.025 +/- 0.006 g.min-1 x mmHg-1 x kg-1). These results suggest that BA perfusion decreased reperfusion edema by attenuating the increase in pulmonary vascular permeability caused by IR injury. Moreover the result in BA-+ lungs suggests that the protective effect was mediated by BA perfusion of PA vasa vasorum rather than bronchopulmonary anastomotic flow, which was trivial compared with PA blood flow.

6-Ketoprostaglandin F1 alpha↗

[Transport and localization of troxerutin in the venous wall].

The vein wall is nourished by diffusion of blood nutrients from the lumen and from the vasa vasorum. It is likely that drugs take the same ways to reach and diffuse through the vessel wall. Thus the uptake of a drug with affinity for the vein wall should give information on its transport to the tissue. This study aimed to explore troxerutin uptake by the long saphenous vein. Troxerutin is a naturally fluorescent flavonoid which has been known to improve subjective signs of patients with chronic venous insufficiency. Nine patients undergoing surgical treatment of varicosis were enrolled in the study. They received for the last 4 days before surgery either 3,500 mg of troxerutin (n = 4) or 1,000 mg twice daily (n = 2). Three patients as controls did not receive any drug. Two samples from thigh and calf long saphenous vein were harvested in each patients and investigated with a confocal laser scanning microscope developed by our institute measuring the fluorescence emitted by troxerutin after excitation by a 458 nm wavelength laser-beam. The intensity of the overall fluorescence was significantly higher in the treated groups (p < 0,001) and slightly higher in the patient who received 3,500 mg of troxerutin than with the lower dosage. The outer wall region provided the highest fluorescence in the treated group while a significant difference was observed in the fluorescence of the medial region between treated and control group. These results showed a marked affinity of troxerutin for the venous wall. The highest uptake in the outer wall region is likely to result from transport through vasa vasorum, owing to the rheologic properties of the drug. The significant medial fluorescence may account for the venous tone improvement with the drug.

Endothelium, Vascular↗

The origin and the progression of varicose veins.

It is proposed that pathological varicosities begin as acute dilator responses of normal veins to noradrenaline released from the vasa vasorum of the vein; the noradrenaline is part of a circulating pool formed by overflow following adrenergic nerve activity. In health, a minimal quantity of noradrenaline routinely flows by reflux to the vasa where it has a negative feedback, venodilator effect. However, when the volume of reflux becomes excessive, the noradrenaline in it abolishes venoconstrictor tone, thereby creating a varicosity. Excessive venous reflux over a short period causes no significant hypoxic damage to the vein wall or any other tissues and any damage associated with it regresses when the excess reflux ceases. However, if excessive reflux is persistent then a time comes when irreversible hypoxic structural changes occur in the vein wall and in other tissues affected by the reflux. The structural pathology associated with varicose veins reflects the effect of the long-term tissue hypoxia associated with that condition.

Animals↗

"Giant pneumoaneurysm" after combined internal carotid artery occlusion and extracranial-intracranial anastomosis.

A patient with a giant aneurysm of the internal carotid artery (ICA) was treated by combined ICA occlusion in the neck and superficial temporal artery to middle cerebral artery anastomosis. Six months after complete closure of the ICA, the patient had episodes of nasal discharge mixed with dark red, old blood. Computed tomographic scan demonstrated that the lumen of the giant aneurysm was filled with a large amount of air, which communicated with the nasal cavity. Not finding a similar case in the literature, we named this entity "giant pneumoaneurysm." After direct operation, the giant pneumoaneurysm collapsed. This unusual complication may be due to a decrease of blood supply to the aneurysmal wall through the vasa vasorum.

Adult↗

The human testicular artery and the pampiniform plexus--where is the connection?

The aim of the study was the microscopic evaluation of the human spermatic cord vessels, with special attention to the connection between the testicular artery and the veins of the pampiniform plexus. We used the corrosive cast method to visualise the angioarchitecture of the spermatic cord. Casts were evaluated using a scanning electron microscope. We observed that there is a narrow space (previously filled with the testicular artery wall), between the casts of the testicular artery and the veins of the pampiniform plexus. This area contains a capillary vessel net, which connects the testicular artery with the veins of the pampiniform plexus. There were no direct anastomoses between the testicular artery and the pampiniform plexus. We hypothesise that the capillary net described is the means of connection between the testicular artery and the pampiniform plexus, and that there can be a testicular artery net of its own vessels (vasa vasorum).

Adult↗

Necrosis and rupture of the aorta and pulmonary trunk in four horses.

Four horses are described with rupture of the aortic arch and pulmonary trunk which resulted in a fistula between these vessels. Ruptures were located near the ligamentum arteriosum. Histological examination of the vessel walls revealed media necrosis which was probably due to intimal thickening and/or medial fibrosis of the vasa vasorum.

Animals↗

Role of medial lamellar architecture in the pathogenesis of aortic aneurysms.

The human abdominal aorta is particularly susceptible to the formation of aneurysms with atrophic walls. This aortic segment normally has fewer medial lamellar units than would be expected for a mammalian aorta of comparable diameter as well as far fewer medial vasa vasorum than would be expected for an aortic wall of comparable thickness. To test the hypothesis that ischemia and/or loss of normal lamellar architecture are predisposing factors for aneurysm formation, we used the pig thoracic aorta, which is furnished with 75 medial layers and vasa supplying the outer two thirds. Vasal blood flow was surgically ablated, and crushing injury was used to reduce the number of intact lamellar units. Mural ischemia alone resulted in necrosis of cells in the medial zone furnished by vasa but did not lead to aneurysmal dilatation, and all the fibrous tissue layers persisted during the 2-month observation period. Mechanical injury resulted in aneurysms in both ischemic and nonischemic aortic segments, but only if fewer than 40 intact lamellae remained and the average tension per lamellar unit exceeded three times the normal value of 1316 +/- 202 dynes/cm (4543 +/- 1624 for ischemic and 4087 +/- 871 for nonischemic segments; p less than 0.01 for each). We conclude that a critical reduction in the number of intact lamellar units results in aneurysmal dilatation. Protracted medial ischemia due to intimal plaque formation in the avascular abdominal aorta may eventually reduce the number of intact lamellae and favor the development of aneurysms.

Animals↗

Parietal centripetal and centrifugal thickening neovascularization in the descending anterior coronary artery. Possible relations with the problem of collateral circulation.

Left coronary arteries of 30 human hearts, obtained at autopsy, were injected with contrast medium. A control group was formed from anterior descending coronary arteries free of atherosclerosis and a study group from anterior descending coronary arteries with areas of atherosclerotic injury. The following differences in the two groups were noted. The control group did not show successfully injected vessels in intima and media, while cases with atherosclerotic injury have them; the number of injected vessels in presence of atherosclerotic injury was three times greater than in healthy coronary arteries; there was a decreasing gradient from outside to in, in the number of injected vessels in both groups; and finally in atherosclerotic vessels we noted a lack of balance between parietal thickening and the residual lumen (conspicuous thickening was accompanied by a small reduction in the lumen). We interpret centrifugal thickening as a possible compensatory mechanism in the major branches for an inadequate canalization of vessel, and suggest possible formation, of coronary collateral circulation from vasa vasorum by a process of neovascularization.

Adult↗

Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation.

A new rabbit model of atherosclerosis is described in which several of the features seen in early human atherosclerosis are generated within a period of 7 days. The positioning of a hollow silastic collar around the carotid artery of a cholesterol-fed rabbit results in macrophage and smooth muscle cell infiltration into the arterial subendothelium, foam cell formation and the deposition of extracellular lipid. A time-dependent accumulation of extracellular cholesteryl ester occurs within the arterial wall. Each of these changes occurs in the presence of a morphologically intact endothelium as assessed using light microscopy, scanning and transmission electron microscopy. A high cholesterol diet did not affect the extent of proliferation but exacerbated cholesteryl ester accumulation. It is proposed that the changes induced by the collar may be mediated by obstruction of the adventitial vasa vasorum with the creation of a localised ischaemic region.

Animals↗

Nonlinear intravascular ultrasound contrast imaging.

Nonlinear contrast agent imaging with intravascular ultrasound (IVUS) is investigated using a prototype IVUS system and an experimental small bubble contrast agent. The IVUS system employed a mechanically scanned single element transducer and was operated at a 20 MHz transmit frequency (F20) for second harmonic imaging (H40), and at a 40 MHz transmit frequency (F40) for subharmonic imaging (SH20). Characterization experiments were performed with agent and tissue phantom signals acquired during transducer rotation. The suppression of transmit frequency tissue signals was achieved using a combination of pulse-inversion and bandpass filtering. H40 was found to improve the contrast-to-tissue signal ratio (CTR) by up to 22 dB relative to F20, but suffered from tissue propagation harmonics at higher pressures (>0.3 MPa). SH20 was also shown to be possible at a range of pressures (approximately 0.25 to 1.8 MPa), with tissue signals suppressed to near the noise floor. Coronary phantom experiments demonstrated the detection of agent in 1 mm diameter vessels outside a larger 4 mm diameter vessel in which the IVUS catheter was situated. These results suggest the feasibility of harmonic IVUS contrast imaging, which may have applications in coronary lumen boundary detection and vasa vasorum imaging.

Blood Vessels↗

The affinity of troxerutin for the venous wall measured by laser scanning microscopy.

The uptake and localization of troxerutin, a trihydroxy-ethyl-rutoside, in the venous wall have been studied in patients undergoing long saphenous vein surgery. Troxerutin, an autofluorescent drug, is currently used to relieve oedema and subjective symptoms in patients with chronic venous insufficiency. In order to determine the localization of the troxerutin, a confocal scanning laser microscope has been used to record the fluorescence from vein cross sections. The quantified fluorescence was used as a measure of the local concentration of troxerutin. In order to reduce the effects of local variation, several images have been scanned from each specimen. Then the recorded data have been analysed to see how the fluorescence varies in the radial direction within the venous wall. Results showed that troxerutin was significantly accumulated in both inner and outer parts of the venous wall. Whereas inner wall troxerutin uptake resulted from direct diffusion through the lumen, the outer wall uptake proceeded likely from the vasa vasorum circulation.

Adult↗

The adventitia, endothelium and atherosclerosis.

Despite many theories, the initiating circumstances for the development of atherosclerosis remain obscure. The development of animal models of atherosclerosis was based upon the different theories of the origins of atherosclerosis which suggested that it originates at the intimal surface of the vessel. A more recent model of atherosclerosis involves perivascular manipulation of the vessel by positioning of a hollow silastic collar around the artery. In this model, several of the features seen in early human atherosclerosis are generated within a period of 7 days. It is hypothesized that arterial wall hypoxia following occlusion of the vasa vasorum may be the initial lesion of atherosclerosis, and hence that in some cases atherosclerosis is a disease of the outer layers of the arterial wall.

Animals↗

The pathogenesis of atheroma and the rationale for its treatment.

Several theories have been proposed to explain the mechanism causing atheroma; these include endothelial cell injury, smooth muscle cell proliferation, lipid deposition and an abnormality of the vasa vasorum. Based on these hypotheses, new therapies aimed at causing regression or preventing the development of atheroma include heparin, calcium antagonists, beta-receptor antagonists, lipid lowering agents and drugs that manipulate platelets.

Animals↗

Aortic dissecting aneurysms: causative factors in 204 subjects.

The pathogenesis of dissecting aneurysms of the aorta is controversial. We reviewed the records of the 204 patients with aortic dissecting aneurysms who underwent autopsy at the John Hopkins Hospital, Baltimore, from 1889 to the present and compared them with age-, race-, and sex-matched controls. The results show that hypertension, Marfan's syndrome, and traumatic, atherosclerotic, or inflammatory injuries of the aortic media are factors associated with dissection. The gross and histologic findings and associated circumstances suggest that most spontaneous aortic dissections originate from tears of the inner layers of the aorta followed by intramural cleavage. In other patients, rupture of the intra-aortic course of branch arteries or vasa vasorum may lead to dissection. Thus, no pathogenetic mechanism is common to all aortic dissections.

Adolescent↗

Histologic fate of the venous coronary artery bypass in dogs.

The histologic fate of venous grafts used for coronary artery bypass has been observed with light and electron microscopy in dogs. Endothelial damage and thrombosis were chiefly limited to the first postoperative week. The muscular media uniformly suffered extensive necrosis and inflammatory cell infiltration during the first week. Its smooth muscle cells either hypertrophied, died or underwent apparent fibroblastic transformation, with eventual fibrous replacement, to a variable degree, of the vein wall. Vascular wall ischemia due to interruption of vasa vasorum during transplantation appears to initiate these medial changes. Much more slowly, intimal thickening by myointimal cells and collagen may reduce the graft lumen to a variable extent.

Animals↗